The germacranes are a diverse class of ten-membered ring sesquiterpenes that includes elephantopin, a cytotoxic component of Elephantopus elatus Bertol. which has shown significant tumor-inhibitory activity against Walker 256 intramuscular carcinosarcoma and P388 lymphocytic leukemia, and costunolide. Both of these compounds, as well as numerous other cyctotoxic sesquiterpenes, contain an alpha-methylene-gamma-lactone moiety; this functionality is thought to be responsible for their biological activity. To date, approaches for the total synthesis of germacranes have met with only limited success. The primary objectives of the proposed research are the following: 1) to develop a general strategy for the synthesis of germacranes based upon the use of sequential Cope-Claisen rearrangements of 2,3-divinylcyclohexanols wherein the less favorable 2,6-cyclodecadienols are irreversibly removed from the Cope equilibrium by Claisen rearrangement to 1,6-cyclodecadienes; 2) to devise a mild, stereospecific procedure for the preparation of alpha-methylene-gamma-lactones employing trimethyl 3-phenylseleno orthopropionate as a masked alpha-substituted acrylic acid equivalent in the Claisen ortho ester rearrangement; 3) to accomplish an enantiospecific total synthesis of (plus)-costunolide in a preliminary investigation of the above strategies; 4) to complete a total synthesis of elephantopin utilizing the sequential Cope-Claisen rearrangements for the construction of the ten-membered ring, the control of stereochemistry, and the introduction of requisite functionality.